Nuclear phosphoprotein phosphatase is involved in the dephosphorylation of nuclear phosphoproteins and this process may have the importance of affecting gene activity. The following studies on this enzyme are proposed: 1. The different forms of the phosphatase will be isolated, and at least one of the major forms will be purified to homogeneity or to the highest attainable specific activity. 2. The properties of the phosphatases will be studied. The subunit structure and the interconvertibility of the multiple forms will be examined with gel electrophoresis and column chromatography as well as by treatment with ethanol or urea. 3. The relationship among the multiple forms and between the nuclear and cytosol phosphatases will be studied by immunochemical techniques using antisera prepared against the purified phosphatase. The substrate specificity will be studied using phosphohistones and different fractions of nuclear nonhistone phosphoproteins as substrates. 5. The effects of metal ions, nucleotides (including cAMP and cGMP), histones, and DNA on the phosphatase activity will be studied to shed light on the possible mechanisms which control the phosphatase activity. BIBLIOGRAPHIC REFERENCES: Tan, E.L., Levine, M.A., Yang, C.S., and Li, H.C. (1976) Effects of ATP and Metal Ions on Cytosol and Nuclear Phosphohistone Phosphatase of Rat Liver. Int. J. Biochem. 7, 21-26. Chou, M.W., Tan, E.L., and Yang, C.S. (1977) Nuclear phosphoprotein phosphatase from calf liver. Fed. Proc. 36 Abstract 2664.